Problem and Significance: According to the CDC global statistics, nearly 1/3 of the world is infected with Tuberculosis (TB). In 2012 8.6 million f peopled infected lived in what is considered a high burden country. Countries such as India, Peru, China, sub Saharan Africa and others have significant regions endemic for TB, particularly among the lower income population. This represents a significant health problem that needs to be addressed. Objective: The objective of this proposal is to characterize and assess a rapid and portable TB treatment monitoring technology based on a solid-state TB sensor that detects volatile organic biomarkers (VOBs) given off by the mycobacterium that cause TB. VOBs are typically found in the breath of human beings and have known associations with many chronic and infectious diseases including TB. The following VOBs are associated with TB: methyl phenylacetate, methyl p-anisate, methyl nicotinate, and o-phenylanisole. Our prior supported research (NSF-STTR) has shown that our newly developed sensor is capable of detecting these VOBs associated in a controlled environment. The sensing material is made up of metal functionalized 3D TiO2 nanotube arrays that bind specific VOBs of interest based on the type of metal present. The readout for the end-user is an electronic signal that gives a rapid, yes/no answer based on change in current (orders of magnitude change). The sensor is simple to use, completely inorganic requiring no specialized biological reagents for sensing (i.e. antibodies, fluorescent tags, etc.), has a long shelf life (over 18 months), uses a simple potentiostat for operation, and is portable. The intended use for this technology is for monitoring TB treatment at the point of care (POC) in a rapid manner to help ascertain if a treatment is working, or help determine if a patient is subject to a drug resistant strain of TB. In addition this sensing platfom integrates a data analytics platform that utilizes the electronics that operate the sensors (smartphone, potentiostat) to collect patient demographics including time and geolocation of the diagnosis to allow health care workers and health departments to map out where TB is located in a population and where it could possibly spread. This type of information in real-time could be invaluable to health departments trying to manage a TB outbreak in a particular region. Using VOBs for monitoring TB treatment is an attractive alternative to traditional methods (i.e. sputum analysis, clinical symptoms), as it is can be detected using non-invasive methods in a rapid manner. Our preliminary results suggest a relationship between levels of VOBs present and if a medication is effective in treating a TB infection (levels appear to reduce in 7-10 days after treatment). Ideally if this relationship holds true, physicians could ascertain if a patient has a drug resistant strain of TB by simply measuring VOBs levels after a week of treatment instead of waiting several weeks for cultures results to get back as is currently done. However, VOBs have seen limited use in POC diagnostics settings since current technology (Gas Chromatography/Mass Spec) for detection of VOBs is expensive and not suitable for low resource setting field use. The technology presented here is low cost and can be tailored to detect VOBs of interest via specific metal functionalization, and can overcome traditional technological hurdles associated with breath analysis. To further develop this technology or TB treatment monitoring and provide comprehensive data analytics to healthcare workers, the following hypothesis and specific aims must be looked at: Hypothesis 1: We hypothesize that the levels of VOBs for TB will decrease if drugs used to treat the infection are effective. Hypothesis 2: We also hypothesize that if the levels of VOBs are not reduced after administering treatment, then this is indicative of multi-drug resistant TB. Specific Aim 1: Determine the analytical validity the TB Breathalyzer device, and determine the sensitivity and specificity of the sensor in reference to the gold standard used to monitor TB. Hypothesis 3: We hypothesize an integrated sensor and smartphone package will integrate into the flow of healthcare for physicians and analysis can be done quickly and easily with an intuitive app for operation and data collection. Specific Aim 2: Integrate sensor into a smartphone package and assess its performance including evaluating the user interface with clinicians to determine how the technology integrates into the flow of health care with physicians. Hypothesis 4: Integration of the sensor with a smartphone controller will allow healthcare professionals to collect data about patient demographics in real time which could provide important information for health care organization in regards to disease prevalence, location, stage of diseases, and effectiveness of treatment. Specific Aim 3: Develop methods for real-time data collection, analysis, and dissemination of the information for epidemiological tracking.